This is a continuing cancer research program that involves coordinated epidemiological, chemical and biological efforts to provide more definitive knowledge as to the etiology of various major cancers. By interrelating human and laboratory research programs, our objective is to provide practical leads to the reduction or elimination of carcinogenic agents from the human environment. The effect on hormone-related--and particularly breast--cancer of long-term estrogen therapy is examined by a number of different epidemiologic and metabolic approaches on humans as well as in laboratory animals. Mammary cancer is one of the most prevalent neoplasms in women and represents 21 percent of all female cancers in the U.S. Although many factors have been implicated, among others, viruses, hormones and chemicals, the causes of mammary cancer are now known. The aim is to study DMBA-induced rat mammary tumor, an experimental model which has been well documented to resemble the human breast tumor. The elucidation of the mechanism of carcinogenesis using this model will provide information which will improve our current understanding of human mammary gland carcinogenesis. Base-line epidemiologic studies continue on a number of major cancers not previously reported as well as special sub-studies, i.e. prostate and pancreas cancer among blacks. Laboratory investigations include a study of the possible carcinogenic effect of smegma, continuing studies on tobacco and tobacco smoke, studies examining the suspected role of high fat diets on mammary carcinogenesis.